Blood Meridian

Tracing Malaria’s Epic War with Humanity

By Matt Windsor

Lori Cormier knew she had to hurry. The young anthropologist had already seen several life-threatening malaria infections during her time among the Guaja hunter-gatherers of the Brazilian Amazon. Seizures were not a good sign.

Malaria requires both mosquito and human hosts to survive. Mosquitoes ingest the parasite that causes malaria when they bite humans or wild primates; the parasites reproduce in the mosquito and travel to its salivary glands, where they infect the mosquito's next victim. In these human or wild primate victims, the parasites enter and reproduce in liver cells, then place male and female versions of themselves in the bloodstream, waiting for the next mosquito bite to start the process again.

“I had brought a few medical supplies with me into the field, and when people were very ill they would come to me,” says Cormier, who was a doctoral student studying the Guaja language and culture in the late 1990s and is now an associate professor in the UAB Department of Anthropology.

Reality Bites

Malaria is caused by a cunning parasite with a complex lifecycle; in fact, it bears an uncanny resemblance to the villains in the Alien movies. Here’s how it works: A female Anopheles mosquito, carrying the parasite Plasmodia in its salivary ducts, bites a human. The parasites move into the person’s bloodstream, where they migrate to liver cells and reproduce. A few days later they emerge in the thousands from each cell and invade nearby red blood cells, where they grow and later burst out again to infect new red blood cells. The process causes high fever, convulsive chills, anemia (not enough red blood cells), and flu-like symptoms, usually 10 days to four weeks after the infection begins. (See “A Vicious Cycle,” below.)

When a five-year-old child was rushed to her hut one morning with seizures, Cormier sprang into action. “I had aspirin, but that doesn’t work fast enough,” she says. “So I ran to the river and soaked a blanket in cold water to try to cool her.” Eventually, the child recovered, but for the rest of her life the fever would threaten to return.

“Perhaps by sheer luck, I never contracted malaria during my year and a half in the field,” says Cormier. “But many of my colleagues who have worked in the Amazon did.” Each year, according to the United Nations agency UNICEF, up to 500 million people are infected with malaria, mainly in Africa and certain parts of Asia and Latin America; 1 million die. Every 30 seconds, a child somewhere in the world dies from malaria.

Every 30 seconds, a child somewhere in the world dies from malaria. In a new book, Cormier explains how the situation could grow worse.

Recipe for an Epidemic

In a new book, The Ten-Thousand Year Fever: Rethinking Human and Wild-Primate Malaria, Cormier explains how those numbers could grow worse. Human encroachment into animal habitats and our blinkered way of thinking about the disease is paving the way for new outbreaks.

But first, Cormier describes how we made malaria into a killer. “Plasmodia are found in a wide variety of mammals, but in most species the infection is generally mild.” The birth of agriculture some 10 millennia ago led to an infectious “Big Bang,” however. It set up “conditions that were ideal for the proliferation of mosquito vectors of malaria,” Cormier says. Clearing land fosters pools of standing water and pulls back the forest canopy to let sunlight stream in, two developments that created a boom in mosquito populations. “Human malaria is not just a biological disease,” Cormier says, “but a biocultural phenomenon.”

It isn’t just about the humans, either. The Ten-Thousand Year Fever forcefully argues that we need to expand our horizons if we hope to avert future malaria epidemics. “We tend to view malaria anthropocentrically, saying that it is a human disease caused by a Plasmodium that is transmitted by a mosquito vector,” Cormier says. But “mosquitoes are not merely vectors, they are co-hosts of malaria, too—and arguably an even more important host than humans from the point of view of the Plasmodia.” The parasite’s key phase of sexual reproduction can only happen inside mosquito hosts.

Host with the Most

Lori Cormier's new book explains how malaria works and how we may be setting the stage for future epidemics by ignoring wild primates as a reservoir for the disease.

Like all living beings, Plasmodia have a prime directive: Keep on living. Evidence suggests that they do so by redirecting the behavior of both their mosquito and human hosts. “Infected mosquitoes become extreme risk-takers,” says Cormier. “Normally, when a mosquito tries to bite a person and is swatted away, it stays away for a time before attempting to sneak a bite again. But infected mosquitoes do not respond to swatting—they keep trying to bite.”

Evidence also suggests that mosquitoes prefer malaria-infected humans—who are carrying parasites ready to begin their lifecycle anew in the mosquito—“and that people suffering from the symptoms of malaria are less likely to defend themselves against mosquitoes,” Cormier says.

Malaria-infected mosquitoes also preferentially target the feet of their human victims, and they seem to prefer children and pregnant women—who have a harder time defending their feet. “They’re going for people who are less able to swat them away,” Cormier says.

Out of the Jungle

Without mosquitoes, malaria would be finished. Without men, however, it can survive, because it has monkeys. Malaria is endemic in wild primates such as apes and monkeys, and mosquitoes can easily carry infections between species, Cormier says. Although human and wild primate malarias have always been considered separately, they are actually closely related, she argues. In fact, wild primates are a natural “reservoir” that can lead to human malaria outbreaks.

A Vicious Cycle

Human and wild-primate malarias are caused by nearly a dozen species of parasite from the genus Plasmodia. There are four primary malaria-causing species, of which P. falciparum is the most dangerous. It is responsible for most of the roughly 1 million deaths per year from malaria in humans.

Plasmodia have a complex lifecycle that requires both mosquitoes and humans or wild primates. The process begins when an infected mosquito takes a bite (this example describes the process in humans, but it is very similar in wild primates).

The parasites, living in the salivary gland of the mosquito, travel into the host and enter the bloodstream in a form called a sporozoite. The sporozoites travel to the liver, where they enter liver cells. Over the next five to 16 days, they grow and divide to produce tens of thousands of merozoites, which then burst out into the bloodstream. (Two species of Plasmodia, P. vivax and P. ovale,also form hypnozoites that can remain dormant in the liver for years and cause relapses when they become active and invade the bloodstream.)

Most of the merozoites infect red blood cells, where they form new merozoites in an accelerating process over one to three days. This is the stage that brings the fever, seizures, and other symptoms of malaria. Some merozoites differentiate into a form called gametocytes, which circulate in the bloodstream in male and female versions—waiting to infect the next mosquito that bites the person.

At the next mosquito bite, the gametocytes travel to the insect’s gut, where the male and female forms combine (through sexual reproduction) to form zygotes, which move into the wall of the mosquito’s gut and become oocysts. Each grows for eight to 15 days, when it ruptures to release thousands of new sporozoites. The sporozoites travel to the mosquito’s salivary glands, ready to infect the next human victim and start the cycle all over again.

Unlike HIV, which spread to humans from wild primates, it’s not always clear which group infected the other with malaria. There is evidence that Old World humans brought malaria to the Western Hemisphere, where mosquitoes transferred the disease to wild primates.

We are more concerned about infections traveling the other direction, of course. And this host-switching is going to become increasingly likely as humans continue to encroach on wild-primate habitats, Cormier says. “When primates lose their habitats, they come in and raid the crops of farmers. Mosquitoes are attracted by those same fields, and they can transfer infection from the monkeys to humans.”

The World Health Organization, responding to malaria’s massive death toll in Africa and other parts of the world, has discussed launching renewed campaigns against mosquitoes, including the possible use of the controversial pesticide DDT. “But if we just focus on malaria as a human disease, we won’t solve the problem,” Cormier says. Without taking wild primates into account, “we will just keep getting infected.”

Back to School

Cormier’s book challenges received wisdom in both biology and anthropology. “People were saying things that didn’t make sense,” she says. “A molecular geneticist was speculating that malaria originated in Neanderthals, but anthropologists find that highly unlikely. At the same time, molecular geneticists find the idea [circulated in an anthropology journal] that malaria came from deer to be highly unlikely. My book tries to connect the dots between fields that aren’t usually connected.”

To find those connections, Cormier took a sabbatical from her faculty position to become a student in several graduate-level courses at UAB, studying tropical infectious diseases and epidemiology among other things. “You can’t become an expert in everything, but you can avoid mistakes that way,” she says. “Anthropology is known as the most interdisciplinary of the disciplines. We wind up in all kinds of fields, from Bedouin poetry to molecular genetics.”

The Ten-Thousand Year Fever is part of a series exploring “historical ecology,” which is “the study of human environmental relationships over time,” says Cormier. “We’re moving away from the idea of ‘man versus nature.’ We’re trying to understand humans as part of the landscape. We’re not just affecting the environment; we are the environment.”